Process for preparation of MR contrast agents
The present invention provides a process for the preparation of an MR contrast agent, said process comprising: i) obtaining a solution in a solvent of a hydrogenatable, unsaturated substrate compound and a catalyst for the hydrogenation of said substrate compound; ii) introducing said solution in droplet form into a chamber containing hydrogen gas (H 2 ) enriched in para-hydrogen (p- 1 H 2 ) and/or ortho-deuterium (o- 2 H 2 ) whereby to hydrogenate said substrate to form a hydrogenated imaging agent; iii) optionally subjecting said hydrogenated imaging agent to a magnetic field having a field strength below earth's ambient field strength; iv) optionally dissolving said imaging agent in an aqueous medium; v) optionally separating said catalyst from the solution of said imaging agent in said aqueous medium; vi) optionally separating said solvent from the solution of said imaging agent in said aqueous medium; and vii) optionally freezing the solution of said imaging agent in said aqueous medium.
1. A process for the preparation of an MR contrast agent comprising:
i) obtaining a solution in a solvent of a hydrogenatable, unsaturated substrate compound and a catalyst for the hydrogenation of said substrate compound; and
ii) introducing said solution in droplet form into a chamber containing hydrogen gas (H 2 ) enriched in para-hydrogen (p- 1 H 2 ) and/or ortho-deuterium (o- 2 H 2 ) to hydrogenate said substrate to form a hydrogenated imaging agent.
2. The process of claim 1 further comprising subjecting said hydrogenated imaging agent to a magnetic field having a field strength at or below the ambient magnetic field strength of the earth.
3. The process of claim 1 further comprising dissolving said imaging agent in an aqueous medium.
4. The process of claim 3 , further comprising separating said catalyst from said solution of imaging agent in aqueous medium.
5. The process of claim 3 , further comprising separating said solvent from said solution of imaging agent in aqueous medium.
6. The process of claim 3 , further comprising freezing said solution of imaging agent in aqueous medium.
7. The process of claim 2 wherein said field strength in step (iii) is less than 50 μT.
8. The process of claim 2 wherein said field strength in step (iii) is less than 1 μT.
9. The process of claim 2 wherein said field strength in step (iii) is less than or equal to 0.1 μT.
10. The process of claim 2 wherein said field strength in step (iii) is cycled in a first part from earth's ambient field strength to a field strength less than 0.1 μT, and in a second part back to ambient field strength again.
11. The process of claim 10 wherein the first part of the cycle is approximately ≦1 ms and the second part is approximately 10-10000 ms.
12. The process of claim 1 wherein said process is carried out directly in water and wherein both said substrate and said catalyst are water-soluble.